Human CD4 + CD103 + cutaneous resident memory T cells are found in the circulation of healthy individuals

• Published in: Science immunology 2019-07, Vol.4 (37)
• Main Authors: Klicznik, Maria M, Morawski, Peter A, Höllbacher, Barbara, Varkhande, Suraj R, Motley, Samantha J, Kuri-Cervantes, Leticia, Goodwin, Eileen, Rosenblum, Michael D, Long, S Alice, Brachtl, Gabriele, Duhen, Thomas, Betts, Michael R, Campbell, Daniel J, Gratz, Iris K
• Format: Article
• Language: English
• ISSN: 2470-9468; 2470-9468
• DOI: 10.1126/sciimmunol.aav8995

Tissue-resident memory T cells (T ) persist locally in nonlymphoid tissues where they provide frontline defense against recurring insults. T at barrier surfaces express the markers CD103 and/or CD69, which function to retain them in epithelial tissues. In humans, neither the long-term migratory behavior of T nor their ability to reenter the circulation and potentially migrate to distant tissue sites has been investigated. Using tissue explant cultures, we found that CD4 CD69 CD103 T in human skin can down-regulate CD69 and exit the tissue. In addition, we identified a skin-tropic CD4 CD69 CD103 population in human lymph and blood that is transcriptionally, functionally, and clonally related to the CD4 CD69 CD103 T population in the skin. Using a skin xenograft model, we confirmed that a fraction of the human cutaneous CD4 CD103 T population can reenter circulation and migrate to secondary human skin sites where they reassume a T phenotype. Thus, our data challenge current concepts regarding the strict tissue compartmentalization of CD4 T cell memory in humans.